Frontiers in Immunology (Sep 2022)

IL27 gene expression distinguishes multisystem inflammatory syndrome in children from febrile illness in a South African cohort

  • Timothy F. Spracklen,
  • Timothy F. Spracklen,
  • Simon C. Mendelsohn,
  • Claire Butters,
  • Claire Butters,
  • Heidi Facey-Thomas,
  • Raphaella Stander,
  • Debbie Abrahams,
  • Mzwandile Erasmus,
  • Richard Baguma,
  • Jonathan Day,
  • Christiaan Scott,
  • Liesl J. Zühlke,
  • Liesl J. Zühlke,
  • Liesl J. Zühlke,
  • George Kassiotis,
  • George Kassiotis,
  • Thomas J. Scriba,
  • Kate Webb,
  • Kate Webb

DOI
https://doi.org/10.3389/fimmu.2022.992022
Journal volume & issue
Vol. 13

Abstract

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IntroductionMultisystem inflammatory syndrome in children (MIS-C) is a severe acute inflammatory reaction to SARS-CoV-2 infection in children. There is a lack of data describing differential expression of immune genes in MIS-C compared to healthy children or those with other inflammatory conditions and how expression changes over time. In this study, we investigated expression of immune-related genes in South African MIS-C patients and controls.MethodsThe cohort included 30 pre-treatment MIS-C cases and 54 healthy non-inflammatory paediatric controls. Other controls included 34 patients with juvenile systemic lupus erythematosus, Kawasaki disease or other inflammatory conditions. Longitudinal post-treatment MIS-C specimens were available at various timepoints. Expression of 80 immune-related genes was determined by real-time quantitative PCR.ResultsA total of 29 differentially expressed genes were identified in pre-treatment MIS-C compared to healthy controls. Up-regulated genes were found to be overrepresented in innate immune pathways including interleukin-1 processing and pyroptosis. Post-treatment follow-up data were available for up to 1,200 hours after first treatment. All down-regulated genes and 17/18 up-regulated genes resolved to normal levels in the timeframe, and all patients clinically recovered. When comparing MIS-C to other febrile conditions, only IL27 expression could differentiate these two groups with high sensitivity and specificity.ConclusionsThese data indicate a unique 29-gene signature of MIS-C in South African children. The up-regulation of interleukin-1 and pyroptosis pathway genes highlights the role of the innate immune system in MIS-C. IL-27 is a potent anti-inflammatory and antiviral cytokine that may distinguish MIS-C from other conditions in our setting.

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